Lea SR, et al. - Herein, researchers sought to determine the impacts of repeated Toll-like receptors (TLRs) 2 and 4 stimulation in COPD alveolar macrophages. Consequent to repetitive stimulation with the same TLR ligand, the occurrence of TLR tolerance in COPD alveolar macrophages was noted, but this only occurred for selected cytokines. Furthermore, no reduction in CXCL8 production was apparent after repetitive TLR stimulation with the same ligand; this may be an important mechanism for the increased CXCL8 levels that have been observed in COPD. No tolerance but enhanced cytokine production was noted as a result of TLR4 stimulation followed by TLR2 stimulation. This may be a relevant mechanism by which bacteria cause excessive inflammation in COPD patients.